Cancers are collectively a very large group of devastating diseases characterized by uncontrolled cell division, growth, invasiveness and the capability of establishing loci on remote sites (metastasis). Cancer cells also escape from a cancer patient's immune system's screening by expressing self-recognition molecular patterns. Cancer cells invade the immune system when they express immune recognition molecular patterns. Cancer metastasizes through the lymph system, the blood stream and through aggressive local tumor expansion.
Cancers are genetic diseases caused by alterations in cells' genetic material, including changes in DNA sequence, chromosome structure and chromosome number. Different types of cancer are usually caused by different genetic changes, although the same genetic change may occur at different parts of human body. On the other hand, similar types of cancer may have similar genetic changes, except for melanoma, which has the most complicated genetic changes. Cancer cells within a tumor are heterogeneous and have unstable genomes. Due to alternations in chromosome structure and chromosome number, tens to thousands of genes are irregularly expressed. It is not surprising that there is little success in developing anti-cancer drugs that target only one or several gene products or pathways.
When a cancer tumor is found early and is accessible by a surgical knife, surgery is still the most effective and reliable way for a potential cure. Surgery usually cuts extra normal tissue surrounding the tumor, aiming to remove 100% cancer cells in the tumor. However, if the cancer has spread or metastasized, or if the cancer occurs in places a surgical knife cannot access, surgery may not be effective due to technical limitations.
Radiotherapy is another local therapy that kills tumors. However, radiotherapy has enormous side effects which include damaging normal tissues adjacent to the cancer tumor, especially tissues in which cells normally divide rapidly such as those in skin, bone marrow, hair follicles and the lining of the mouth, esophagus, and intestines. Such damages in cells' genetic material may lead to cancer recurrence, new cancer or both. Radiotherapy usually takes about 3 weeks to kill cancer cells in a tumor. However, radiotherapy will not be effective when a cancer tumor is too big or cancer cells have spread.
Other local therapies including cryosurgery and UV local therapy are similar to surgery or radiotherapy, and may be applied to limited parts of the human body.
Intratumoral injection of chemotherapy drugs such as cisplatin is a new method of delivering chemotherapy drugs locally to kill the tumor when its corresponding chemotherapy drug could not kill tumors under the physiologically tolerable dose. However, because chemotherapy drugs are usually small molecules that cannot be confined to the local area, substantial adverse effects, beyond those occurred in systemic chemotherapy, are unavoidable.
Chemotherapy drugs usually target DNA molecules in actively dividing cells in both cancer and normal cells. Thus they do not work against solid-tumors under the safe physiological dose and have side effects which include damage to actively dividing normal cells. Other systemic therapies including immunotherapy, hormonal therapy and gene therapy may be employed to kill cancer cells that have spread. However, just like chemotherapy, these therapies are not effective against solid-tumor cancer cells with different antigens or mutations. Thus, when the metastasis has a few solid-tumors, a combination of systemic and local therapies including surgery, radiotherapy, chemotherapy and immunotherapy are employed according to the cancer type, staging (cancer tumor size, nodal involvement, metastatic progression and pathological classification), and the health status of the patient.
Unfortunately, in many metastases, too many solid-tumors are left for any existing local therapies to handle and, on average, more than 1000 cancer patients die each day in the US alone. There is a great need to find new therapies that can eliminate multiple solid-tumors locally with few side effects.